Herein, with CD44 recycling between the cell surface and interior of tumor cells, an MSC-based “Trojan horse” loaded with PTX/HA-PLGA polymeric micelles (MSC-micelles) is fabricated to gain deeper tumor penetration and more active-targeting for orthotopic glioma therapy to overcome non-specific distribution attributed to the wide expression of CD44 on endothelial cells, epithelial cells, fibroblasts, keratinocytes, and leukocytes delivered by PTX/HA-PLGA micelles [17]. This evidence concerns the gene CD44 and central nervous system cancer.